Validation of US-induced thermal strain imaging (TSI) technique to detect lipid contents in carotid artery plaques is proposed. Plaques characterized by a large lipid core and a thin fibrous cap have been identified as vulnerable plaques, or rupture-prone plaques. Identification of these potentially fatal plaques before their disruption is clinically desirable and will help predict vascular risk and guide therapies. Current imaging methods for identifying high risk features of plaque are either invasive or limited. TSI may provide alternative imaging technique to non-invasively and reliably identify and characterize atherosclerotic plaques (APs). Lipids have a negative temperature dependence of the sound speed, whereas water-based tissues have positive temperature dependence. TSI uses heating to induce a temperature rise in tissue and then determines the temperature change from local changes in sound speed using a phase-sensitive, correlation-based speckle tracking algorithm. TSI features strong contrast between lipids and water-based tissues, which stems primarily from sound speed contrast. The fundamental concept and feasibility has been demonstrated by several groups in the last decade mostly in vitro. For practicality and reliability of TSI in clinic, controlled heating source is important. We propose US-induced TSI using a single linear probe connected to a commercial ultrasound system. The overall goal proposed in this study is to develop and evaluate US-induced TSI to characterize carotid plaques. The fundamental hypotheses are: 1. An US linear probe can be designed and integrated into a commercial US imaging system to provide controlled US energy delivery to tissue to induce and image thermal strain 2. Within AP, the local TSI contrast indicates the presence of local lipid core and TSI intensity map measures lipid concentration and distribution. 3. US-induced TSI can provide a robust, reliable, and noninvasive tool for characterizing an AP, and in particular assessing its quantity of lipid, which is an important component that confers vulnerability. This technique should be easily translatable into a clinical tool for the diagnosis and management of carotid vulnerable plaques. A wide range of technical and scientific issues must be investigated to fully exploit the capabilities and practicality of the techniques proposed. Therefore, the three specific aims of this application are: 1. Develop an optimized US heating source fully integrated with an US imaging system to provide controlled energy delivery to tissue during routine US scanning. 2. Develop a robust US heating/imaging pulse sequence and data acquisition scheme. 3. Establish the relationship between US- induced TSI and the histopathology of APs, especially the assessment of the lipid core. This correlation will serve as an indication of the feasibility of applying this technique as a localized plaque characterization tool. The study will include computer simulations for beamforming and tissue thermal model, water tank experiments using the tissue mimicking phantoms, the human tissue specimens from autopsy, amputation and carotid endarterectomy (CEA), and high cholesterol-fed rabbit model.